Ovarian cancer with BRCA1 mutation may be treatable with arthritis drug

Auranofin – a gold-containing drug used to treat rheumatoid arthritis – could potentially improve the prognosis for ovarian cancer patients with a faulty BRCA1 gene, according to new lab research.

The study found treatment with auranofin reduced survival of ovarian cancer cells with faulty BRCA1 genes.

The study – by researchers at the University of Plymouth in the UK, working with the nearby Plymouth Oncology Centre at Derriford Hospital – is published in the journal Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.

BRCA1 is a protein that repairs DNA. If there is a mutation in the gene that codes for it, it can lead to an insufficient amount of the protein, which results in DNA damage not being repaired. This increases the chance that affected cells will develop further gene alterations and become cancerous.

Mutations in BRCA1 increase the risk of developing ovarian andbreast cancers. BRCA1 is mutated in 15-20% of ovarian cancers.

Previous studies have also suggested that breast and ovarian cancers that have BRCA1 mutations may also be more sensitive to drugs that damage DNA – the cancer cells may more easily succumb to the drugs.

Auranofin is currently undergoing trials for repurposing to treat recurrent epithelial ovarian cancer, which accounts for around 90% of diagnosed ovarian cancers.

Using already-available drugs such as auranofin to treat cancer is highly promising because their effects on the body are well documented, notes corresponding author Awadhesh Jha, professor of toxicology and associate head (research) in Plymouth’s School of Biological Sciences.

Survival of BRCA1-depleted cancer cells reduced by up to 37%

Prof. Jha and colleagues investigated the effect of auranofin on ovarian cancer cells grown in the lab.

They found that lack of BRCA1 protein rendered the cells more vulnerable to auranofin, compared with ovarian cancer cells with normal versions of the gene.

Moreover, the lab tests showed that BRCA1-depleted ovarian cancer cells treated with auranofin suffered more irreparable damage – in the form of lethal DNA double-strand breaks.

For the study, the team tested auranofin on two types of ovarian cancer cell – OVCAR5 and SKOV3 – with BRCA1 expression levels depleted and compared the results with a control set.

They found that even before BRCA1 depletion, the SKOV3 cells were already relatively sensitive to auranofin, and with BRCA1 depletion, the survival of the cancer cells was reduced by up to 37%, with an auranofin concentration of 1 part per million.

“It suggests that auranofin has the potential to be considered for future clinical studies to treat such ovarian cancers and this could serve as the springboard to use other available drugs which are not used as chemotherapeutic drugs.”